Proof of Concept Trial of Dronabinol in Obstructive Sleep Apnea

<h4>Study objective</h4>Animal data suggest that Δ(9)-TetraHydroCannabinol (Δ(9)THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ(9)THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA).<h4>Design and setting</h4>Proof of concept; single-center dose-escalation study of dronabinol.<h4>Participants</h4>Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment.<h4>Intervention</h4>Dronabinol was administered after baseline PSG, starting at 2.5 mg once daily. The dose was increased weekly, as tolerated, to 5 mg and finally to 10 mg once daily.<h4>Measurements and results</h4>Repeat PSG assessments were performed on nights 7, 14, and 21 of dronabinol treatment. Change in AHI (ΔAHI, mean ± SD) was significant from baseline to night 21 (-14.1 ± 17.5; p = 0.007). No degradation of sleep architecture or serious adverse events was noted.<h4>Conclusion</h4>Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5-10 mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.